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      Comparative metabolomics of aging in a long-lived bat: Insights into the physiology of extreme longevity

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          Abstract

          Vespertilionid bats (Mammalia: Order Chiroptera) live 3–10 times longer than other mammals of an equivalent body size. At present, nothing is known of how bat fecal metabolic profiles shift with age in any taxa. This study established the feasibility of using a non-invasive, fecal metabolomics approach to examine age-related differences in the fecal metabolome of young and elderly adult big brown bats ( Eptesicus fuscus) as an initial investigation into using metabolomics for age determination. Samples were collected from captive, known-aged big brown bats ( Eptesicus fuscus) from 1 to over 14 years of age: these two ages represent age groups separated by approximately 75% of the known natural lifespan of this taxon. Results showed 41 metabolites differentiated young (n = 22) and elderly (n = 6) Eptesicus. Significant differences in metabolites between young and elderly bats were associated with tryptophan metabolism and incomplete protein digestion. Results support further exploration of the physiological mechanisms bats employ to achieve exceptional longevity.

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          METLIN: a metabolite mass spectral database.

          Endogenous metabolites have gained increasing interest over the past 5 years largely for their implications in diagnostic and pharmaceutical biomarker discovery. METLIN (http://metlin.scripps.edu), a freely accessible web-based data repository, has been developed to assist in a broad array of metabolite research and to facilitate metabolite identification through mass analysis. METLINincludes an annotated list of known metabolite structural information that is easily cross-correlated with its catalogue of high-resolution Fourier transform mass spectrometry (FTMS) spectra, tandem mass spectrometry (MS/MS) spectra, and LC/MS data.
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            A senescent cell bystander effect: senescence-induced senescence

            Summary Senescent cells produce and secrete various bioactive molecules including interleukins, growth factors, matrix-degrading enzymes and reactive oxygen species (ROS). Thus, it has been proposed that senescent cells can damage their local environment, and a stimulatory effect on tumour cell growth and invasiveness has been documented. However, it was unknown what effect, if any, senescent cells have on their normal, proliferation-competent counterparts. We show here that senescent cells induce a DNA damage response, characteristic for senescence, in neighbouring cells via gap junction-mediated cell–cell contact and processes involving ROS. Continuous exposure to senescent cells induced cell senescence in intact bystander fibroblasts. Hepatocytes bearing senescence markers clustered together in mice livers. Thus, senescent cells can induce a bystander effect, spreading senescence towards their neighbours in vitro and, possibly, in vivo.
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              HMDB 3.0—The Human Metabolome Database in 2013

              The Human Metabolome Database (HMDB) (www.hmdb.ca) is a resource dedicated to providing scientists with the most current and comprehensive coverage of the human metabolome. Since its first release in 2007, the HMDB has been used to facilitate research for nearly 1000 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 3.0) has been significantly expanded and enhanced over the 2009 release (version 2.0). In particular, the number of annotated metabolite entries has grown from 6500 to more than 40 000 (a 600% increase). This enormous expansion is a result of the inclusion of both ‘detected’ metabolites (those with measured concentrations or experimental confirmation of their existence) and ‘expected’ metabolites (those for which biochemical pathways are known or human intake/exposure is frequent but the compound has yet to be detected in the body). The latest release also has greatly increased the number of metabolites with biofluid or tissue concentration data, the number of compounds with reference spectra and the number of data fields per entry. In addition to this expansion in data quantity, new database visualization tools and new data content have been added or enhanced. These include better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps. This article describes these enhancements to the HMDB, which was previously featured in the 2009 NAR Database Issue. (Note to referees, HMDB 3.0 will go live on 18 September 2012.).
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 May 2018
                2018
                : 13
                : 5
                : e0196154
                Affiliations
                [1 ] Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, Ohio, The United States of America
                [2 ] Musculoskeletal Biology Group, Northeast Ohio Medical University, Rootstown, Ohio, The United States of America
                [3 ] Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, Canada
                [4 ] Department of Foods and Human Nutritional Sciences, University of Manitoba, Duff Roblin Building, Winnipeg, Canada
                Instituto Butantan, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-3595-2485
                Article
                PONE-D-17-37671
                10.1371/journal.pone.0196154
                5929510
                29715267
                71f3120f-ac1a-4c32-b078-d9094e713efb
                © 2018 Ball et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 October 2017
                : 6 April 2018
                Page count
                Figures: 3, Tables: 2, Pages: 20
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000001, National Science Foundation;
                Award ID: NSF-CMMI 1537745
                Award Recipient :
                This research was supported by the National Science Foundation [grant number NSF-CMMI 1537745 to L.N.C.]. The opinions, findings and conclusions expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Bats
                People and Places
                Population Groupings
                Age Groups
                Elderly
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolomics
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolites
                Medicine and Health Sciences
                Geriatrics
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Amino Acids
                Aromatic Amino Acids
                Tryptophan
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Amino Acids
                Aromatic Amino Acids
                Tryptophan
                Biology and Life Sciences
                Biochemistry
                Proteins
                Amino Acids
                Aromatic Amino Acids
                Tryptophan
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Amino Acid Metabolism
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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